title: Multivariable analysis of outcome predictors and adjustment of main outcome results to baseline data profile in randomized controlled trials: Safe Implementation of Thrombolysis in Stroke-MOnitoring STudy (SITS-MOST).
abstract: OBJECTIVE
  The Safe Implementation of Thrombolysis in Stroke-MOnitoring STudy (SITS-MOST) unadjusted results demonstrated that intravenous alteplase is well tolerated and that the effects were comparable with those seen in randomized, controlled trials (RCTs) when used in routine clinical practice within 3 hours of ischemic stroke onset. We aimed to identify outcome predictors and adjust the outcomes of the SITS-MOST to the baseline characteristics of RCTs.
  
  
  METHODS
  The study population was SITS-MOST (n=6483) and pooled RCTs (n=464) patients treated with intravenous alteplase within 3 hours of stroke onset. Multivariable, backward stepwise regression analyses (until P<or=0.10) were performed to identify the outcome predictors for SITS-MOST. Variables appearing either in the final multivariable model or differing (P<0.10) between SITS-MOST and RCTs were included in the prediction model for the adjustment of outcomes. Main outcome measures were symptomatic intracerebral hemorrhage, defined as National Institutes of Health Stroke Scale deterioration >or=1 within 7 days with any hemorrhage (RCT definition), mortality, and independency as defined by modified Rankin Score of 0 to 2 at 3 months.
  
  
  RESULTS
  The adjusted proportion of symptomatic intracerebral hemorrhage for SITS-MOST was 8.5% (95% CI, 7.9 to 9.0) versus 8.6% (6.3 to 11.6) for pooled RCTs; mortality was 15.5% (14.7 to 16.2) versus 17.3% (14.1 to 21.1); and independency was 50.4% (49.6 to 51.2) versus 50.1% (44.5 to 54.7), respectively. In the multivariable analysis, older age, high blood glucose, high National Institutes of Health Stroke Scale score, and current infarction on imaging scans were related to poor outcome in all parameters. Systolic blood pressure, atrial fibrillation, and weight were additional predictors of symptomatic intracerebral hemorrhage. Current smokers had a lower rate of symptomatic intracerebral hemorrhage. Disability before current stroke (modified Rankin Score 2 to 5), diastolic blood pressure, antiplatelet other than aspirin, congestive heart failure, patients treated in new centers, and male sex were related to high mortality at 3 months.
  
  
  CONCLUSIONS
  The adjusted outcomes from SITS-MOST were almost identical to those in relevant RCTs and reinforce the conclusion drawn previously in the unadjusted analysis. We identified several important outcome predictors to better identify patients suitable for thrombolysis.
authors.affiliation: Department of Neurology, Karolinska University Hospital-Solna, Karolinska Institutet, Stockholm, Sweden. nils.wahlgren@karolinska.se
authors.forename: Nils
authors.initials: N
authors.lastname: Wahlgren
authors.forename: Niaz
authors.initials: N
authors.lastname: Ahmed
authors.forename: Niclas
authors.initials: N
authors.lastname: Eriksson
authors.forename: Franz
authors.initials: F
authors.lastname: Aichner
authors.forename: Erich
authors.initials: E
authors.lastname: Bluhmki
authors.forename: Antoni
authors.initials: A
authors.lastname: Dávalos
authors.forename: Terttu
authors.initials: T
authors.lastname: Erilä
authors.forename: Gary A
authors.initials: GA
authors.lastname: Ford
authors.forename: Martin
authors.initials: M
authors.lastname: Grond
authors.forename: Werner
authors.initials: W
authors.lastname: Hacke
authors.forename: Michael G
authors.initials: MG
authors.lastname: Hennerici
authors.forename: Markku
authors.initials: M
authors.lastname: Kaste
authors.forename: Martin
authors.initials: M
authors.lastname: Köhrmann
authors.forename: Vincent
authors.initials: V
authors.lastname: Larrue
authors.forename: Kennedy R
authors.initials: KR
authors.lastname: Lees
authors.forename: Thomas
authors.initials: T
authors.lastname: Machnig
authors.forename: Risto O
authors.initials: RO
authors.lastname: Roine
authors.forename: Danilo
authors.initials: D
authors.lastname: Toni
authors.forename: Geert
authors.initials: G
authors.lastname: Vanhooren
mesh_terms: D000203:Activities of Daily Living; D000368:Aged; D002543:Cerebral Hemorrhage / Q000139:chemically induced / Q000453:epidemiology; D015897:Comorbidity; D003953:Diagnosis-Related Groups; D005260:Female; D005343:Fibrinolytic Agents / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D005500:Follow-Up Studies; D006801:Humans; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D018579:Patient Selection; D011379:Prognosis; D016032:Randomized Controlled Trials as Topic / Q000706:statistics & numerical data*; D012042:Registries; D012307:Risk Factors; D012720:Severity of Illness Index; D020521:Stroke / Q000188:drug therapy* / Q000401:mortality; D015912:Thrombolytic Therapy / Q000009:adverse effects / Q000706:statistics & numerical data*; D010959:Tissue Plasminogen Activator / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D016896:Treatment Outcome
chemical_list: D005343:Fibrinolytic Agents; D010959:Tissue Plasminogen Activator